Is PAX8 p.Pro167= (c.501C>A) pathogenic?

PAX8 p.Pro167= (c.501C>A) is classified Conflicting classifications of pathogenicity in PAX8 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-02-01). Low-frequency (popmax 1.13%, sas); Associated with hypothyroidism, congenital, nongoitrous, 2.

What condition is associated with PAX8 p.Pro167= (c.501C>A)?

PAX8 p.Pro167= (c.501C>A) is associated with hypothyroidism, congenital, nongoitrous, 2 (ClinVar).

How common is PAX8 p.Pro167= (c.501C>A) in the general population?

PAX8 p.Pro167= (c.501C>A) is low-frequency (popmax 1.13%, sas) (gnomAD).

PAX8 p.Pro167=

c.501C>A · rs61730086 · VCV330892

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.13%, sas)

Conditions

hypothyroidism, congenital, nongoitrous, 2

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.28	GERP -3.2, phastCons 0.95
Overall
CADD	3.579	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.13% South Asian · 1,032/90,988 alleles

Filtering AF 1.08% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.05%

Overall 0.0682% 1,101/1,613,498 alleles · low-frequency exomes 1,048/1,461,192 · genomes 53/152,306 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	1.13%	88
Remaining individualsnot grpmax-eligible	0.072%	1,389
Admixed American	0.005%	20,001
African / African-American	0.00267%	37,519
East Asian	0.00223%	44,860
European (non-Finnish)	0.00153%	65,529

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PAX8
Protein: p.Pro167=
Coding: c.501C>A
MANE Select: NM_003466
dbSNP: rs61730086
Type: single nucleotide variant
Location: chr2:113242108 (GRCh38)

Full PAX8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hypothyroidism, congenital, nongoitrous, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/pax8-p-pro167 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown